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Background: Aldosterone antagonists have proven efficacy for management of resistant hypertension and proteinuria reduction; however, they are not widely used due to risk of hyperkalemia. This study assesses the risk factors for hyperkalemia in patients with chronic kidney disease (CKD) and resistant hypertension whose blood pressure (BP) is reduced to a guideline goal. Methods: This is a two-center study conducted in university-based hypertension clinics directed by clinical hypertension specialists. Forty-six patients with resistant hypertension and stages 2 or 3 CKD (mean estimated glomerular filtration rate (eGFR) 56.5 ± 16.2 ml/min/1.73 m²) were evaluated for safety and efficacy of aldosterone blockade added to preexisting BP-lowering regimens. All patients were on three mechanistically complementary antihypertensive agents including a diuretic and a renin-angiotensin system blocker. Patients were evaluated after a median of 45 treatment days. The primary endpoint was change in systolic BP. Secondary endpoints included change in serum potassium, creatinine, eGFR, diastolic BP and tolerability. Results: The mean age of the patients studied was 64.9 ± 10.7 years, all were obese and 86% had type 2 diabetes, with 82% being African-American. Addition of aldosterone antagonism yielded a further mean reduction in systolic BP of 14.7 ± 5.1 mm Hg (p = 0.001). Females with BMI >30 and those with a baseline systolic BP >160 mm Hg were more likely to have a greater BP reduction to aldosterone antagonism. In total, 39% of the patients had a >30% decrease in eGFR when the BP goal was achieved. The mean increase in serum potassium was 0.4 mEq/l above baseline (p = 0.001), with 17.3% manifesting hyperkalemia, i.e. serum potassium >5.5 mEq/l. Predictors of hyperkalemia included a baseline eGFR of ≤45 ml/min/1.73 m² in whom serum potassium was >4.5 mEq/l on appropriately dosed diuretics. Contributing risks in this subgroup included a systolic BP reduction of >15 mm Hg associated with an eGFR fall of >30%. Conclusion: Aldosterone antagonism is effective and safe for achieving a BP goal among people with diabetic nephropathy when added to a triple antihypertensive regimen that includes a blocker of the renin-angiotensin system and an appropriately selected and dosed diuretic. Caution is advised when using aldosterone blockade for BP control in people with advanced stage 3 nephropathy with a serum potassium of >4.5 mEq/l for safety reasons.

Background and objectives: Acute kidney injury (AKI) is associated with adverse outcomes in critically ill patients. The influence of preexisting chronic kidney disease (CKD) on AKI outcomes is unclear.Design, setting, participants, & measurements: We analyzed data from a prospective observational cohort study of AKI in critically ill patients who received nephrology consultation: the Program to Improve Care in Acute Renal Disease. In-hospital mortality rate, length of stay, and dialysis dependence were compared in patients with and without a prior history of CKD, defined by an elevated serum creatinine, proteinuria, and/or abnormal renal ultrasound within a year before hospitalization. We hypothesized that patients with AKI and prior history of CKD would have lower mortality rates, shorter lengths of stay, and higher rates of dialysis dependence than patients without prior history of CKD.Results: Patients with AKI and a prior history of CKD were older and underwent nephrology consultation earlier in the course of AKI. In-hospital mortality rate was lower (31 versus 40%, P ‫؍‬ 0.04), and median intensive care unit length of stay was 4.6 d shorter (14.7 versus 19.3 d, P ‫؍‬ 0.001) in patients with a prior history of CKD. Among dialyzed survivors, patients with prior CKD were also more likely to be dialysis dependent at hospital discharge. Differences in outcome were most evident in patients with lower severity of illness.Conclusions: Among critically ill patients with AKI, those with prior CKD experience a lower mortality rate but are more likely to be dialysis dependent at hospital discharge. Future studies should determine optimal strategies for managing AKI with and without a prior history of CKD.

Microalbuminuria, originally described more than 3 decades ago as a predictor of nephropathy in patients who had type 1 diabetes mellitus and associated with higher cardiovascular risk, is now linked with increased risk for cardiovascular events rather than progression to end-stage kidney disease. This article reviews the role of microalbuminuria in the context of atherosclerotic vascular disease. It presents the methods for microalbuminuria assessment in clinical practice, its relations with other cardiovascular risk factors, and the pathophysiologic associations between microalbuminuria and vascular damage. In addition, this article discusses the prognostic significance of microalbuminuria for cardiovascular disease as well as existing therapeutic interventions for reducing urine albumin excretion in patients who are at high cardiovascular risk.

W hile the majority of participants in clinical trials demonstrate the benefits of the thiazide-like diuretic, chlorthalidone (CTD), 1 hydrochlorothiazide (HCTZ) is prescribed more frequently in the United States. 2 Only one large outcome trial, the Multiple Risk Factor Intervention Trial (MRFIT), used both HCTZ and CTD, but no head-to-head comparisons were performed. In MRFIT, after about 5 years patients who received each diuretic as initial therapy were compared against the common "referred care" group. For patients who used CTD as initial therapy, there was a trend indicating lower mortality compared with those using HCTZ. Use of CTD declined after research studies using high doses suggested an increased risk of cardiovascular deaths and a high incidence of hypokalemia. 3 A recent review suggests that few differences exist between HCTZ and CTD-thus, they should be considered interchangeable. 4 These authors state, however, that there are differences in duration of action and pharmacology between the two agents. Based on these differences, we propose that the same dose of CTD when substituted for HCTZ may result in an additional systolic blood pressure (SBP) reduction and help achieve blood pressure (BP) goals in patients already receiving three or more medications. OBSERVATIONSA consecutive chart review from the Rush University Hypertension Center sought patients with the following inclusion criteria: age over 40 years, not at target BP for medical condition (<140/90 mm Hg and <130/80 mm Hg for those with kidney disease or diabetes), and on a stable antihypertensive regimen that included the same dose of HCTZ for at least 6 months. All patients underwent recording of two sitting BP readings. Nineteen of the 2000 charts (≈1%) screened met the inclusion criteria. The average of two seated BP readings from the initial visit and the follow-up (after the switch) were analyzed. Following the initial visit, patients were switched from HCTZ to CTD at the same daily dose without any further changes in their antihypertensive regimen. No patients received K + supplementation before or after the change. Laboratory data for serum K + and kidney function, as well as clinical data for BP and pulse rates, were recorded at follow-up visits. Patients were also asked about symptoms related to gout at each visit.Seventeen of the 19 patients were taking 25 mg of HCTZ at the index visit; two were taking a dose of 12.5 mg/d (Table). SBP values before and after the diuretic switch are shown for individual patients in the Figure. If two patients are eliminated, i.e., those with baseline SBPs of 220 mm Hg that decreased to 156 mm Hg and 194 mm Hg that decreased to 148 mm Hg, an overall median difference of 4 mm Hg instead of 7 mm Hg in SBP was noted (p=0.052). Six of the 19 who originally had uncontrolled hypertension achieved their individual BP targets after the change in medication. Serum K + levels from eight of the 19 patients were not significantly different (3.9±0.3 mEq/L on HCTZ vs. 4.0±0.4 mEq/L on CTD). Only one of these pat...